INJECTABLE MICROFOAM CONTAINING A SCLEROSING AGENT

Abstract: Injectable microfoam for sclerotherapy. The sclerotherapy of varices is based on the injection of liquid substances capable of suppressing them. The present invention relates to the preparation of sclerosing substances in the form of a microfoam. The microfoam is prepared with sclerosing agents, and is then injected in the vein to be treated, so that the microfoam displaces the blood contained in the vein and provides for the contact of the sclerosing agent with the vascular endothelium, with a predetermined known concentration and during a controllable time.

Description: State of the art Sclerosis of varicose veins is based on the injection into the veins of liquid substances which, by causing a localized inflammatory reaction, favours the elimination of these abnormal veins. When a sclerosing liquid is injected, it is mixed with the blood contained in the vein and is diluted in an unknown proportion. The results are uncertain (owing to over- or under-dosage) and are limited to short varicose segments. As the size of the varicose veins to be injected decreases, this dilution is less and the results obtained are more predictable. Nowadays sclerosis is a technique selected in cases of small and medium varicose veins, those with diameters equal to or greater than 7 mm being treated by surgery. At present, sclerosis and surgery complement one another but sclerosis treatment continues not to be applicable to large varicose veins. In these large varicose veins, if a sclerosing substance is injected, its concentration in the vein, its homogeneous distribution in the blood, and the time for which it is in contact with the internal walls of the vessel treated are not known. In 1946, Orbach injected a few cubic centimetres of air into small varicose veins and confirmed a displacement of the blood inside the vessel which was occupied by the injected air. The sclerosing solution introduced immediately afterwards was more effective than if it had been injected into the blood. In thick varicose veins, when air is injected the phenomenon described of the displacement of the blood by the injected air does not occur but the air forms a bubble inside the vein which makes the method ineffective in these vessels. The same author had the idea, a few years later, of injecting foam obtained by agitation of a container containing sodium tetradecyl sulphate, which is an anionic sclerosing detergent with a good foaming capability. The method was of little use owing to the large size of the bubbles formed and was dangerous owing to the side effects of atmospheric nitrogen which is only slightly soluble in blood. Both methods had limited practical repercussion being used only in small varicose veins. Description of the invention This invention relates to the preparation of An injectable micro-foam for therapeutic uses, prepared or for preparation as required, characterized in that the micro-foam is produced with any sclerosing substance.. According to the present invention, it has been discovered that if a micro-foam of a pharmacologically inert, sterile, physiological serum is injected in a horizontal position, the micro-foam causes displacement of the blood contained in the vessel, including the most expanded varicose veins, on account of the low pressure of the blood contained therein in the horizontal. The elevation of the member injected reduces the venous pressure even more facilitating the filling of the vein exclusively with micro-foam, which remains in the vessel as long as the patient does not get up from the operating table. If the micro-foam produced with the physiological serum is replaced by micro-foam produced with a sclerosing substance and injected into the vein, it displaces the blood contained in the vein and ensures that the sclerosing agent contacts the endothelium of the vessel in a known concentration and for a controllable time, achieving sclerosis of the entire segment occupied. The advantages of this method allow: 1. the concentration of the sclerosing agent in the vessel to be known, since the micro-foam displaces the blood and is not diluted therein like a liquid; 2. homogeneous distribution of the sclerosis product therein to be insured; 3. the time for which it is kept in contact with the internal walls of the vein to be controlled; none of which factors is known precisely or is controllable with the use of liquid sclerosing agents. The present invention can be implemented by the preparation of a micro-foam with any sclerosing substance such as: polidocanol, sodium tetradecyl sulphate, hypertonic glucose or gluco-saline solutions, chromic glycerol, ethanolamine oleate, sodium morrhuato, or iodic solutions. Further therapeutic uses of the injectable micro-foam of the invention are given in Claims 9 to 12. Once the sclerosing micro-foam has been produced by any of the existing methods, of which two are described below, it is introduced into any sterile container which can serve for subsequent injection into the veins to be treated and which permits stability of the foam in a form which can be extracted by means of a syringe or any other instrument which facilitates its injection into the vessels to be treated. Example 1: The sclerosing micro-foam was produced by mixing in a sterile, hermetic container connected, if desired, to a pressure bottle of oxygen, or a mixture of oxygen and carbon dioxide or other physiological gases; mechanical beating was carried out by means of a micro-motor which rotated a brush immersed in the sclerosing solution to be foamed. The micro-foam was produced by beating at between 8,000 and 15,000 rpm for a period of between 60 and 120 seconds. It was introduced into any container which could later serve for its storage and its subsequent injection into the vessels to be sclerosed. If the sclerosing substance does not have a foaming capability, polysorbate 20, polysorbate 80, polygelina or any other substance with a foaming capability accepted as inert for intravenous use is added. Example 2: The sclerosing substance was introduced into a hermetic, pressurized and sterile container and the micro-foam was produced by stirring the solution with discharge from the container for subsequent use.

Claims: An injectable micro-foam for therapeutic uses, prepared or for preparation as required, characterized in that the micro-foam is produced with any sclerosing substance. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the sclerosing substance is polidocanol. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the sclerosing substance is sodium tetradecyl sulphate. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the sclerosing substance is a hypertonic glucose or gluco-saline solution. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the substance used is chromic glycerol. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the substance used is ethanolamine oleate. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the substance used is sodium morrhuate. An injectable micro-foam for therapeutic uses according to claim 1, characterized in that the substance used is any iodic solution. An injectable micro-foam for therapeutic uses according to the preceding claims for use in phlebology. An injectable micro-foam for therapeutic uses according to claims 1 to 8, for use in the treatment of oesophageal varices. An injectable micro-foam for therapeutic uses according to claims 1 to 8, for use in proctology. An injectable micro-foam for therapeutic uses according to claims 1 to 8, for use in angiology. A method for the preparation of an injectable micro-foam for use in therapy characterised in that it comprises producing a micro-foam with a sclerosing substance. A method as claimed in claim 13 characterised in that the sclerosing substance is a polidocanol, sodium tetradecyl sulphate, hypertonic glucose or gluco-saline solution, chromic glycerol, ethanolamine oleate, sodium morrhuato or iodic solution. A micro-foam for use in therapy characterised in that it is obtainable by beating a sclerosing solution with a micromotor rotated brush at 8,000 to 15,000 r.p.m. for 60 to 120 seconds.

Inventors: CABRERA GARCIA-OLMEDO JUAN, CABRERA GARRIDO JUAN, CABRERA GARCIA-OLMEDO, JUAN, CABRERA GARRIDO, JUAN
Applicants: BTG INT LTD, BTG INTERNATIONAL LIMITED
Application year: 1994
Main classification: A61K9
IPC codes: A61K9